Messenger RNA (mRNA) based therapeutics have shown great promise for expressing functional antibodies and proteins. Clinical studies have explored mRNA for use as vaccines through local administration of naked mRNA or mRNA-transfected dendritic cells in order to induce antigen-specific immune responses. Recently, extensive efforts have been devoted to achieving the systemic delivery of mRNA using liposomes, polymeric nanoparticles, and mRNA-protein complexes. Although significant advances have been made, new mRNA carriers are needed in order to improve delivery efficiency and maximize therapeutic windows of mRNA therapeutics in different human conditions.
Previously, lipid-like nanoparticles (LLNs) have demonstrated efficient delivery of small interfering RNA (siRNA) in rodents and nonhuman primates. siRNA and mRNA possess common physicochemical properties, including components of nucleic acids and negative charges; therefore, LLNs may also serve well as mRNA delivery materials. However, lipid-like nanoparticle (LLN)-assisted mRNA delivery is relatively unexplored and understanding of this system is very limited.
The compounds, compositions, and methods disclosed herein address these and other needs.